Development and validation of a HPLC-UV method for 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), a toxic metabolite of haloperidol, in humans: Providing in vivo evidence of CYP3A4-mediated CPHP formation
- Authors
- Park, J.-Y.; Shin, J.-G.
- Issue Date
- 2016
- Publisher
- Korean Society Clinical Pharmacology and Therapeutics
- Keywords
- CPHP; CYP3A4; Haloperidol; HPLC
- Citation
- Translational and Clinical Pharmacology, v.24, no.3, pp.147 - 151
- Indexed
- SCOPUS
KCI
- Journal Title
- Translational and Clinical Pharmacology
- Volume
- 24
- Number
- 3
- Start Page
- 147
- End Page
- 151
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/91400
- DOI
- 10.12793/tcp.2016.24.3.147
- ISSN
- 2289-0882
- Abstract
- We developed a high-performance liquid chromatographic procedure for the determination of 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), a toxic metabolite of haloperidol, in human. Chromatographic analysis was performed on a reverse-phase C18 column with a mobile phase containing 50 mM potassium phosphate buffer/acetonitrile (75: 25, vol/vol) using UV detection with a wavelength of 220 nm. The limits of detection for CPHP were 1 ng/ml in urine and the assay was linear over the concentration range of 2-500 ng/ml for urine. This analytical method was applied to measure CPHP in human. Nineteen healthy subjects were enrolled and all subjects received a single oral dose of 5 mg haloperidol following a treatment of placebo or itraconazole at 200 mg/day for 10 days in a randomized crossover manner. CPHP was detected in urine samples and average recovered amount of CPHP was 81.31 µg/24 hr in the placebo phase and it was significantly reduced to 30.34 µg/24 hr after itraconazole treatment. The finding provides in vivo evidence that CPHP is an in vivo metabolite of haloperidol in human and its formation is mediated by CYP3A4. © 2016 Translational and Clinical Pharmacology.
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